[IL-2/IL-2R pathway in dendritic cell modulates both their cytokine synthesis profiles and their capacity to activate allogeneic CD4+ T lymphocytes]. / La voie IL-2/IL-2R chez la cellule dendritique module à la fois leur synthèse de cytokines et leur capacité à activer des lymphocytes T CD4+ allogéniques.

The results provide new insights into the role of IL-2/IL-2R pathway in DC. We report that stimulation of human monocyte-derived DC with LPS strongly upregulated CD25 (α chain of the IL-2R) expression. In addition, by using a humanized monoclonal antibody against CD25, we demonstrated that the IL-2 signalling in DC upregulated both IL-12 and γIFN production but decreased IL-10 synthesis. Anti-CD25 treatment reduced the ability of LPS-DC to induce allogeneic CD4(+) T cell proliferation as compared to LPS-matured DC. In addition, LPS-matured DC treated with IL-2 had a higher allostimulatory capacity compared to LPS-DC. We also found that LPS-matured DC produced IL-2. Thus, IL-2 seems to contribute actively to DC activation through an autocrine pathway. Moreover, IL-2 pathway in DC is involved in T helper priming. These findings might be useful for protocols in cellular therapy and a valuable tool to understand graft rejection versus the acquisition of peripheral tolerance.

Anti-CD25 antibodies decrease the ability of human dendritic cells to prime allogeneic CD4 T cells.

Anti-CD25 monoclonal antibodies are largely used in clinical transplantation to prevent acute allograft rejection episodes. Although their effects on T lymphocytes have been extensively studied, their impact on human dendritic cells (DCs) has been less reported. Furthermore, the role of the interleukin-2 in DC functions has not yet been fully elucidated. In this study, we observed that stimulation of human monocyte-derived DCs with lipopolysa ccharide or CD40L strongly induced the expression of CD25. We showed that pretreatment of DC with anti-CD25 diminished their ability to prime T-helper cells. In contrast, humanized anti-CD25 monoclonal antibodies did not affect the up-regulation of CD86, CD80, CD83, HLA-DR, or CD40 induced by lipopolysaccharide stimulation. This study supported previously unrecognized effects of anti-CD25 monoclonal antibodies on DCs that may contribute to their clinical efficacy.

Anti-CD25 antibodies affect cytokine synthesis pattern of human dendritic cells and decrease their ability to prime allogeneic CD4+ T cells.

Anti-CD25 monoclonal antibodies are widely used in clinical transplantation to prevent acute allograft rejection. Although their effects on T lymphocytes have been extensively studied, their impact on human dendritic cells (DC) has never been reported. Furthermore, the role of the IL-2 in DC functions has not yet been fully elucidated. In this study, we confirm that the stimulation of human monocyte-derived DC with LPS strongly induced the expression of CD25 and that LPS-matured DC also expressed the beta and gamma chain of the IL-2R. We also showed that adding anti-CD25 monoclonal antibodies to LPS induced a decrease in IL-12, IL-1, TNF-alpha, IL-6, and IFN-gamma production and an increase in IL-10 synthesis by DC compared with stimulation with LPS alone. Furthermore, we showed that these modifications diminished the T helper priming ability of DC and polarized the alloimmune response toward TH2. In contrast, humanized anti-CD25 monoclonal antibodies did not affect the up-regulation of CD86, CD80, CD83, HLADR, or CD40 induced upon LPS stimulation. Taken together, this study discloses some previously unrecognized effects of anti-CD25 monoclonal antibodies on DC that may contribute to their clinical efficacy. In addition, this study also shed some light on the role of the IL-2 in human DC activation.